The synergistic interaction between the calcineurin B subunit and IFN-γ enhances macrophage antitumor activity.

Abstract:

:Macrophages are involved in tumor growth and progression. They infiltrate into tumors and cause inflammation, which creates a microenvironment favoring tumor growth and metastasis. However, certain stimuli may induce macrophages to act as tumor terminators. Here we report that the calcineurin B subunit (CnB) synergizes with IFN-γ to make macrophages highly cytotoxic to cancer cells. Furthermore, CnB and IFN-γ act synergistically to polarize mouse tumor-associated macrophages, as well as human monocyte-derived macrophages to an M1-like phenotype. This synergy is mediated by the crosstalk between CnB-engaged integrin αM-p38 MAPK signaling and IFN-γ-initiated p38/PKC-δ/Jak2 signaling. Interestingly, the signal transducer and activator of transcription 1 (STAT1) is a key factor that orchestrates the synergy of CnB and IFN-γ, and the phosphorylation status at Ser727 and Tyr701 of STAT1 is directly regulated by CnB and IFN-γ.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Su Z,Yang R,Zhang W,Xu L,Zhong Y,Yin Y,Cen J,DeWitt JP,Wei Q

doi

10.1038/cddis.2015.92

subject

Has Abstract

pub_date

2015-05-07 00:00:00

pages

e1740

issn

2041-4889

pii

cddis201592

journal_volume

6

pub_type

杂志文章
  • SPATS2, negatively regulated by miR-145-5p, promotes hepatocellular carcinoma progression through regulating cell cycle.

    abstract::Spermatogenesis associated serine rich 2 (SPATS2) has been reported to contribute to the tumorigenesis of multiple malignancies. The molecular function of SPATS2 in hepatocellular carcinoma (HCC) is still not fully understood. In this study, we aimed to investigate the expression pattern and function roles of SPATS2 i...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03039-y

    authors: Dong G,Zhang S,Shen S,Sun L,Wang X,Wang H,Wu J,Liu T,Wang C,Wang H,Lu T,Rao B,Ren Z

    更新日期:2020-10-09 00:00:00

  • The hedgehog and Wnt/β-catenin system machinery mediate myofibroblast differentiation of LR-MSCs in pulmonary fibrogenesis.

    abstract::Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease that is characterized by enhanced changes in stem cell differentiation and fibroblast proliferation. Resident mesenchymal stem cells (LR-MSCs) can undergo phenotype conversion to myofibroblasts to augment extracellular matrix producti...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0692-9

    authors: Chen X,Shi C,Cao H,Chen L,Hou J,Xiang Z,Hu K,Han X

    更新日期:2018-05-29 00:00:00

  • Period1 mediates rhythmic metabolism of toxins by interacting with CYP2E1.

    abstract::The biological clock is an endogenous biological timing system, which controls metabolic functions in almost all organs. Nutrient metabolism, substrate processing, and detoxification are circadian controlled in livers. However, how the clock genes respond to toxins and influence toxicity keeps unclear. We identified t...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03343-7

    authors: Ge W,Wang T,Zhao Y,Yang Y,Sun Q,Yang X,Gao Y,Xu X,Zhang J

    更新日期:2021-01-12 00:00:00

  • AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages.

    abstract::Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondr...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.211

    authors: Six E,Lagresle-Peyrou C,Susini S,De Chappedelaine C,Sigrist N,Sadek H,Chouteau M,Cagnard N,Fontenay M,Hermine O,Chomienne C,Reynier P,Fischer A,André-Schmutz I,Gueguen N,Cavazzana M

    更新日期:2015-08-13 00:00:00

  • RASSF1A inhibits PDGFB-driven malignant phenotypes of nasopharyngeal carcinoma cells in a YAP1-dependent manner.

    abstract::Nasopharyngeal carcinoma (NPC) is a highly aggressive tumor characterized by distant metastasis. Deletion or down-regulation of the tumor suppressor protein ras-association domain family protein1 isoform A (RASSF1A) has been confirmed to be a key event in NPC progression; however, little is known about the effects or ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03054-z

    authors: Liang YY,Deng XB,Lin XT,Jiang LL,Huang XT,Mo ZW,Yuan YW,Teh MT

    更新日期:2020-10-14 00:00:00

  • LncRNA KCNQ1OT1 regulates proliferation and cisplatin resistance in tongue cancer via miR-211-5p mediated Ezrin/Fak/Src signaling.

    abstract::Numerous findings have demonstrated that long noncoding RNA (lncRNA) dysregulation plays a key role in many human neoplasms, including tongue squamous cell carcinoma (TSCC), yet the potential mechanisms of lncRNAs in chemo-resistance remain elusive. Our research showed that the lncRNA KCNQ1OT1 was upregulated in chemo...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0793-5

    authors: Zhang S,Ma H,Zhang D,Xie S,Wang W,Li Q,Lin Z,Wang Y

    更新日期:2018-07-03 00:00:00

  • CCT3 acts upstream of YAP and TFCP2 as a potential target and tumour biomarker in liver cancer.

    abstract::Although Yes-associated protein (YAP) is very important to liver cancer, its nuclear localisation prevents consideration as a promising therapeutic target and a diagnostic biomarker. Recently, we reported that the protumourigenic roles of YAP in liver cancer are indispensable for transcription factor CP2 (TFCP2) in a ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1894-5

    authors: Liu Y,Zhang X,Lin J,Chen Y,Qiao Y,Guo S,Yang Y,Zhu G,Pan Q,Wang J,Sun F

    更新日期:2019-09-09 00:00:00

  • Pharmacologic inhibition of reactive gliosis blocks TNF-α-mediated neuronal apoptosis.

    abstract::Reactive gliosis is an early pathological feature common to most neurodegenerative diseases, yet its regulation and impact remain poorly understood. Normally astrocytes maintain a critical homeostatic balance. After stress or injury they undergo rapid parainflammatory activation, characterized by hypertrophy, and incr...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.277

    authors: Livne-Bar I,Lam S,Chan D,Guo X,Askar I,Nahirnyj A,Flanagan JG,Sivak JM

    更新日期:2016-09-29 00:00:00

  • The epigenetically regulated miR-494 associates with stem-cell phenotype and induces sorafenib resistance in hepatocellular carcinoma.

    abstract::Hepatocellular carcinoma (HCC) represents the second cause of cancer-related mortality worldwide and is associated with poor prognosis, especially in patients not amenable for curative treatments. The multi-kinase inhibitor sorafenib represents the first-line treatment option for advanced HCC; nevertheless, its effect...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0076-6

    authors: Pollutri D,Patrizi C,Marinelli S,Giovannini C,Trombetta E,Giannone FA,Baldassarre M,Quarta S,Vandewynckel YP,Vandierendonck A,Van Vlierberghe H,Porretti L,Negrini M,Bolondi L,Gramantieri L,Fornari F

    更新日期:2018-01-05 00:00:00

  • LncRNA Hoxaas3 promotes lung fibroblast activation and fibrosis by targeting miR-450b-5p to regulate Runx1.

    abstract::Long noncoding RNAs (lncRNAs) participate in organ fibrosis and various pulmonary diseases, but its role in idiopathic pulmonary fibrosis (IPF) is not fully understood. In this study, we found lncRNA Hoxaas3 (Hoxaas3) was up-regulated in the mice model of BLM-induced PF and TGF-β1-induced fibrogenesis in lung fibrobla...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02889-w

    authors: Lin S,Zhang R,Xu L,Ma R,Xu L,Zhu L,Hu J,An X

    更新日期:2020-08-26 00:00:00

  • NR2C2-uORF targeting UCA1-miR-627-5p-NR2C2 feedback loop to regulate the malignant behaviors of glioma cells.

    abstract::Accumulating evidence has highlighted the potential role of non-coding RNAs (ncRNAs) and upstream open-reading frames (uORFs) in the biological behaviors of glioblastoma. Here, we elucidated the function and possible molecular mechanisms of the effect of some ncRNAs and NR2C2-uORF on the biological behaviors of glioma...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1149-x

    authors: Fan Z,Zheng J,Xue Y,Liu X,Wang D,Yang C,Ma J,Liu L,Ruan X,Wang Z,Liu Y

    更新日期:2018-12-05 00:00:00

  • Flavones hydroxylated at 5, 7, 3' and 4' ameliorate skin fibrosis via inhibiting activin receptor-like kinase 5 kinase activity.

    abstract::Skin fibrosis is mainly characterized by excessive collagen deposition. Studies have recently identified a number of flavonoids with variable structures that have the potency of inhibiting collagen synthesis and thus attenuating organ fibrosis. In this study, we found that flavones with 5, 7, 3', 4' hydroxy substituti...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1333-7

    authors: Zhang Y,Wang J,Zhou S,Xie Z,Wang C,Gao Y,Zhou J,Zhang X,Li Q

    更新日期:2019-02-11 00:00:00

  • From computational modelling of the intrinsic apoptosis pathway to a systems-based analysis of chemotherapy resistance: achievements, perspectives and challenges in systems medicine.

    abstract::Our understanding of the mitochondrial or intrinsic apoptosis pathway and its role in chemotherapy resistance has increased significantly in recent years by a combination of experimental studies and mathematical modelling. This combined approach enhanced the quantitative and kinetic understanding of apoptosis signal t...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/cddis.2014.36

    authors: Würstle ML,Zink E,Prehn JH,Rehm M

    更新日期:2014-05-29 00:00:00

  • NMI inhibits cancer stem cell traits by downregulating hTERT in breast cancer.

    abstract::N-myc and STAT interactor (NMI) has been proved to bind to different transcription factors to regulate a variety of signaling mechanisms including DNA damage, cell cycle and epithelial-mesenchymal transition. However, the role of NMI in the regulation of cancer stem cells (CSCs) remains poorly understood. In this stud...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.200

    authors: Feng X,Xu X,Xiao X,Zou K,Yu W,Wu J,Tang R,Gao Y,Hao J,Zhao X,Liao Y,Chen Y,Huang W,Guo W,Kang L,Deng W

    更新日期:2017-05-11 00:00:00

  • Circular RNA FAM114A2 suppresses progression of bladder cancer via regulating ∆NP63 by sponging miR-762.

    abstract::Numerous evidences have shown that circular RNAs (circRNAs) play a key role in regulating the pathogenesis of cancer. However, the mechanism of circRNAs in urothelial carcinoma of bladder (UCB) remains largely unclear. In this study, we found circFAM114A2 was significantly downregulated both in UCB tissue specimens an...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2226-5

    authors: Liu T,Lu Q,Liu J,Xie S,Feng B,Zhu W,Liu M,Liu Y,Zhou X,Sun W,Zhang Y,Chen X,Fang F,Guo H,Yang R

    更新日期:2020-01-22 00:00:00

  • 4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis.

    abstract::4-hydroxyphenylpyruvate dioxygenase (HPD) is an important modifier of tyrosine metabolism. However, the precise contribution of HPD to cancer metabolism and tumorigenesis remains unclear. In this study, we found that HPD was highly expressed in lung cancer and its higher expression correlated with poor prognosis in lu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1756-1

    authors: Shan C,Lu Z,Li Z,Sheng H,Fan J,Qi Q,Liu S,Zhang S

    更新日期:2019-07-08 00:00:00

  • Continued 26S proteasome dysfunction in mouse brain cortical neurons impairs autophagy and the Keap1-Nrf2 oxidative defence pathway.

    abstract::The ubiquitin-proteasome system (UPS) and macroautophagy (autophagy) are central to normal proteostasis and interdependent in that autophagy is known to compensate for the UPS to alleviate ensuing proteotoxic stress that impairs cell function. UPS and autophagy dysfunctions are believed to have a major role in the pat...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.443

    authors: Ugun-Klusek A,Tatham MH,Elkharaz J,Constantin-Teodosiu D,Lawler K,Mohamed H,Paine SM,Anderson G,John Mayer R,Lowe J,Ellen Billett E,Bedford L

    更新日期:2017-01-05 00:00:00

  • Inhibition of Casein kinase-2 induces p53-dependent cell cycle arrest and sensitizes glioblastoma cells to tumor necrosis factor (TNFα)-induced apoptosis through SIRT1 inhibition.

    abstract::Glioblastoma multiforme (GBM) are resistant to TNFα-induced apoptosis and blockade of TNFα-induced NF-κB activation sensitizes glioma cells to apoptosis. As Casein kinase-2 (CK2) induces aberrant NF-κB activation and as we observed elevated CK2 levels in GBM tumors, we investigated the potential of CK2 inhibitors (CK2...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2012.10

    authors: Dixit D,Sharma V,Ghosh S,Mehta VS,Sen E

    更新日期:2012-02-09 00:00:00

  • Gefitinib targets ZAP-70-expressing chronic lymphocytic leukemia cells and inhibits B-cell receptor signaling.

    abstract::Chronic lymphocytic leukemia (CLL) can be divided into groups based on biomarkers of poor prognosis. The expression of the tyrosine kinase ZAP-70 (member of the Syk tyrosine kinase family) in CLL cells is associated with shorter overall survival in CLL patients. Currently, there is a lack of targeted therapies for pat...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.391

    authors: Dielschneider RF,Xiao W,Yoon JY,Noh E,Banerji V,Li H,Marshall AJ,Johnston JB,Gibson SB

    更新日期:2014-10-02 00:00:00

  • EZH2-mediated epigenetic suppression of long noncoding RNA SPRY4-IT1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition.

    abstract::Recent evidence indicates that long noncoding RNAs (lncRNAs) have a critical role in the regulation of cellular processes such as differentiation, proliferation, and metastasis. These lncRNAs are dysregulated in a variety of cancers and many function as tumor suppressors; however, the regulatory factors involved in si...

    journal_title:Cell death & disease

    pub_type: 临床试验,杂志文章

    doi:10.1038/cddis.2014.256

    authors: Sun M,Liu XH,Lu KH,Nie FQ,Xia R,Kong R,Yang JS,Xu TP,Liu YW,Zou YF,Lu BB,Yin R,Zhang EB,Xu L,De W,Wang ZX

    更新日期:2014-06-26 00:00:00

  • Aquaporin 3 maintains the stemness of CD133+ hepatocellular carcinoma cells by activating STAT3.

    abstract::An increasing interest in liver cancer stemness arises owing to its aggressive behavior and poor prognosis. CD133, a widely known liver cancer stem cell marker, plays critical roles in the maintenance of liver cancer stemness. Thus, exploring the regulatory mechanism of CD133 expression is significant. In the present ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1712-0

    authors: Wang Y,Wu G,Fu X,Xu S,Wang T,Zhang Q,Yang Y

    更新日期:2019-06-13 00:00:00

  • Astrocytes are important mediators of Aβ-induced neurotoxicity and tau phosphorylation in primary culture.

    abstract::Alzheimer's disease (AD) is pathologically characterised by the age-dependent deposition of β-amyloid (Aβ) in senile plaques, intraneuronal accumulation of tau as neurofibrillary tangles, synaptic dysfunction and neuronal death. Neuroinflammation, typified by the accumulation of activated microglia and reactive astroc...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2011.50

    authors: Garwood CJ,Pooler AM,Atherton J,Hanger DP,Noble W

    更新日期:2011-06-02 00:00:00

  • Novel ADAM-17 inhibitor ZLDI-8 enhances the in vitro and in vivo chemotherapeutic effects of Sorafenib on hepatocellular carcinoma cells.

    abstract::Hepatocellular carcinoma (HCC) is one of the greatest life threats for Chinese people, and the prognosis of this malignancy is poor due to the strong chemotherapy resistance in patients. Notch pathway components mediate cell survival and epithelial-mesenchymal transition (EMT), and also participate in the induction of...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0804-6

    authors: Zhang Y,Li D,Jiang Q,Cao S,Sun H,Chai Y,Li X,Ren T,Yang R,Feng F,Li BA,Zhao Q

    更新日期:2018-07-03 00:00:00

  • MiR-485-3p and miR-485-5p suppress breast cancer cell metastasis by inhibiting PGC-1α expression.

    abstract::Breast cancer is the worldwide leading cause of cancer mortality in women. The majority of deaths from breast cancer arise from metastasis of local tumors. Cancer cells support their rapid proliferation by diverting metabolites into anabolic pathways, but during cancer metastasis, the proliferative program of invasive...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.27

    authors: Lou C,Xiao M,Cheng S,Lu X,Jia S,Ren Y,Li Z

    更新日期:2016-03-24 00:00:00

  • miR-491-5p-induced apoptosis in ovarian carcinoma depends on the direct inhibition of both BCL-XL and EGFR leading to BIM activation.

    abstract::We sought to identify miRNAs that can efficiently induce apoptosis in ovarian cancer cells by overcoming BCL-X(L) and MCL1 anti-apoptotic activity, using combined computational and experimental approaches. We found that miR-491-5p efficiently induces apoptosis in IGROV1-R10 cells by directly inhibiting BCL-X(L) expres...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.389

    authors: Denoyelle C,Lambert B,Meryet-Figuière M,Vigneron N,Brotin E,Lecerf C,Abeilard E,Giffard F,Louis MH,Gauduchon P,Juin P,Poulain L

    更新日期:2014-10-09 00:00:00

  • Continuous exposure of pancreatic cancer cells to dietary bioactive agents does not induce drug resistance unlike chemotherapy.

    abstract::The repeated treatment of cancer cells with chemo- or radiotherapy induces therapy resistance, but it was previously unknown whether the same effect occurs upon continuous exposure of cancer cells to diet-derived chemopreventive agents. We elucidated this interesting question in pancreatic ductal adenocarcinoma, which...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.157

    authors: Fan P,Zhang Y,Liu L,Zhao Z,Yin Y,Xiao X,Bauer N,Gladkich J,Mattern J,Gao C,Schemmer P,Gross W,Herr I

    更新日期:2016-06-02 00:00:00

  • MEIS2 is essential for neuroblastoma cell survival and proliferation by transcriptional control of M-phase progression.

    abstract::MEIS2 has an important role in development and organogenesis, and is implicated in the pathogenesis of human cancer. The molecular basis of MEIS2 action in tumorigenesis is not clear. Here, we show that MEIS2 is highly expressed in human neuroblastoma cell lines and is required for neuroblastoma cell survival and prol...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.370

    authors: Zha Y,Xia Y,Ding J,Choi JH,Yang L,Dong Z,Yan C,Huang S,Ding HF

    更新日期:2014-09-11 00:00:00

  • cBid, Bax and Bcl-xL exhibit opposite membrane remodeling activities.

    abstract::The proteins of the Bcl-2 family have a crucial role in mitochondrial outer membrane permeabilization during apoptosis and in the regulation of mitochondrial dynamics. Current models consider that Bax forms toroidal pores at mitochondria that are responsible for the release of cytochrome c, whereas Bcl-xL inhibits por...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.34

    authors: Bleicken S,Hofhaus G,Ugarte-Uribe B,Schröder R,García-Sáez AJ

    更新日期:2016-02-25 00:00:00

  • Interplay between Caspase 9 and X-linked Inhibitor of Apoptosis Protein (XIAP) in the oocyte elimination during fetal mouse development.

    abstract::Mammalian female fertility is limited by the number and quality of oocytes in the ovarian reserve. The number of oocytes is finite since all germ cells cease proliferation to become oocytes in fetal life. Moreover, 70-80% of the initial oocyte population is eliminated during fetal and neonatal development, restricting...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-2019-x

    authors: Liu X,Castle V,Taketo T

    更新日期:2019-10-17 00:00:00

  • Treatment response, survival, safety, and predictive factors to chimeric antigen receptor T cell therapy in Chinese relapsed or refractory B cell acute lymphoblast leukemia patients.

    abstract::This study aimed to evaluate treatment response, survival, safety profiles, and predictive factors to chimeric antigen receptor T cell (CAR-T) therapy in Chinese patients with relapsed or refractory B cell acute lymphoblast leukemia (R/R B-ALL). 39R/R B-ALL patients who underwent CAR-T therapy were included. Baseline ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2388-1

    authors: Li L,Liu J,Xu M,Yu H,Lv C,Cao F,Wang Z,Fu Y,Zhang M,Meng H,Zhang X,Kang L,Zhang Z,Li J,Feng J,Lian X,Yu L,Zhou J

    更新日期:2020-03-30 00:00:00